1ll9
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Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With Amoxicillin
OverviewOverview
beta-lactamases confer resistance to beta-lactam antibiotics such as, penicillins and cephalosporins. However, beta-lactams that form an, acyl-intermediate with the enzyme but subsequently are hindered from, forming a catalytically competent conformation seem to be inhibitors of, beta-lactamases. This inhibition may be imparted by specific groups on the, ubiquitous R(1) side chain of beta-lactams, such as the, 2-amino-4-thiazolyl methoxyimino (ATMO) group common among, third-generation cephalosporins. Using steric hindrance of deacylation as, a design guide, penicillin and carbacephem substrates were converted into, effective beta-lactamase inhibitors and antiresistance antibiotics. To, investigate the structural bases of inhibition, the crystal structures of, the acyl-adducts of the penicillin substrate amoxicillin and the new, analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds, in a catalytically incompetent conformation resembling that adopted by, third-generation cephalosporins, demonstrating the transferability of such, sterically hindered groups in inhibitor design.
About this StructureAbout this Structure
1LL9 is a Single protein structure of sequence from Escherichia coli with AXL as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Using steric hindrance to design new inhibitors of class C beta-lactamases., Trehan I, Morandi F, Blaszczak LC, Shoichet BK, Chem Biol. 2002 Sep;9(9):971-80. PMID:12323371
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